Considerable evidence exists that a mineralocorticoid other than aldosterone is an important factor in a proportion of patients with the syndrome of low-renin hypertension. There is also evidence that considerable heterogeneity may exist in the mineralocorticoid produced in this syndrome and several steroids have been implicated. Most recently, 19-nor-deoxycorticosterone (19-nor-DOC), a potent mineralocorticoid, has been identified as a naturally-occurring substance in man and rat, and it or its precursor(s) have been shown to be elevated in experimental and genetic hypertension in the rat and in hypertensive man. The recently-described pathway for the production of 19-nor-DOC strongly suggests the existence of other nor-corticosteroids. We will determine the possible existence of other 19-nor-corticoids (namely, 19-nor-B, 19-nor-A, 19-nor-prog, 19-nor-18-OH-DOC) in experimental and genetic animal models (adrenal regeneration hypertension and spontaneously hypertensive rat) and, by studying the time-course excretion pattern and mineralocorticoid properties of these steroids, relate their significance to the development or perpetuation of the hypertension. We will also determine the tissue of origin of the 19-nor-corticoids by studying the conversion of labelled adrenal precursors (19-oxo and 19-oic precursor) to the corresponding nor-steroid. By biosynthesis of these labelled nor-steroids, we will determine if specific receptors are present in the aorta, kidney, and heart of the rat. It is our belief that alterations in the excretion of these and other nor-corticoids may be related to the hypertensive diathesis in the sodium-surfeit state in both experimental and human hypertension and that tissues distal to the adrenal play a role in the production of these nor-steroids.